Squamous cell carcinoma of the tonsils: a molecular analysis of HPV associations

Clin Cancer Res. 2002 Apr;8(4):1093-100.


Background: The role of human papilloma virus (HPV) in the pathogenesis and biological behavior of tonsillar squamous cell carcinoma (TSCC) are areas of intense investigation.

Methods: This study used PCR analysis to identify HPV in paraffin-embedded tonsillar and nodal tissue from 52 patients with TSCC and 48 age (+/-5 year)/gender-matched controls with benign tonsillar hyperplasia. Results were correlated with HLA-DRB1 haplotype and clinical outcome.

Results: HPV was identified in 46% of patients with TSCC and 6% of controls. DNA sequencing showed the presence of HPV type 16 in 21 patients (40%) with TSCC. There was no statistically significant association between HLA-DRB1 expression and TSCC or HPV infection. Fifteen of 16 patients with HPV-positive TSCC with regional metastases had evidence of HPV in pathologically involved lymph nodes. In eight HPV 16-positive TSCC patients with lymph node metastasis, PCR testing identified HPV 16 in 17 of 23 histologically negative lymph nodes. Patients with HPV-positive TSCC without metastatic disease had no evidence of HPV in their lymphatic tissue. Clinically, HPV-associated carcinoma was present in younger patients in comparison with HPV-negative TSCC patients (mean age, 56.6 versus 66 years; P = 0.001). The odds for patients with HPV infection to develop TSCC were 18.2 times greater than for patients without HPV infection (95% confidence interval 4.6, 73.1). There was no statistically significant association between presence of HPV and cause-specific survival (hazard ratio = 2.5 for HPV negative versus positive; P = 0.26), after adjusting for age in a Cox proportional hazards regression analysis.

Conclusion: HPV is an independent risk factor for TSCC. Identification of HPV in the histologically positive and negative lymph nodes of patients with HPV-positive TSCC/metastatic disease supports the role of HPV in the oncogenesis of TSCC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alcohol Drinking
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / virology
  • Case-Control Studies
  • DNA, Viral / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Papillomaviridae / genetics
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Risk Factors
  • Smoking
  • Survival Analysis
  • Tonsillar Neoplasms / genetics
  • Tonsillar Neoplasms / pathology*
  • Tonsillar Neoplasms / virology
  • Tumor Virus Infections / genetics
  • Tumor Virus Infections / pathology
  • Tumor Virus Infections / virology


  • DNA, Viral
  • HLA-DR Antigens
  • HLA-DRB1 Chains